Role of calcium in the hormonal regulation of liver metabolism

Williamson, John; Cooper, Ronald H.; Hoek, Jan B.

doi:10.1016/0304-4173(81)90012-4

Cited by 316 publications

(95 citation statements)

References 395 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in fig.3, the half-maximal concentration of vasopressin required for inhibition of glucagon-induced CAMP formation was about 8 x lo-" M. In contrast, Ca'+-mobilisation and phosphorylase activation (which results from the increased cytosolic Ca*+ level [6,13]) require a 5-fold greater concentration of vasopressin for half-maximal effects [ 13,181. Indeed, cytosolic Ca2+ is not significantly increased by the dose of vasopressin which mediates half-maximal effects on CAMP accumulation ( fig.…”

Section: Resultsmentioning

confidence: 99%

“…There is much evidence that the metabolic responses to vasopressin in liver directly result from cellular Ca" mobilisation and elevation of cytosolic Ca2' [6]. Since inhibition of glucagon-induced CAMP formation has also been demonstrated in rat hepatocytes incubated in the presence of the Ca2+ ionophore A23 187 [5,7], it is possible that increases in cytosolic Ca2+ may play a primary role in CAMP inhibition by vasopressin, perhaps as a result of activation of Ca2+-calmodulin-dependent cAMP phosphodiesterase [g] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Studies on the mechanism of inhibition of hepatic cAMP accumulation by vasopressin

1983

View full text Add to dashboard Cite

Vasopressin elicited a dose‐dependent inhibition of glucagon‐induced cAMP accumulation in isolated hepatocytes. This response was not diminished by incubation of cells with the calmodulin antagonists trifluoperazine or chlorpromazine and was only slightly reduced in Ca2+‐depleted hepatocytes. Half‐maximal inhibition of cAMP accumulation occurred at 8 × 10‐11 M vasopressin, a dose which does not increase cytosolic Ca2+ in hepatocytes. Direct activation of adenylate cyclase by forskolin was significantly inhibited by vasopressin in Ca2+‐depleted cells. It is concluded that inhibition of hormone‐induced cAMP accumulation by vasopressin in liver is not dependent on cellular Ca2+ mobilisation but may involve direct inhibition of adenylate cyclase.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Studies on the mechanism of inhibition of hepatic cAMP accumulation by vasopressin

1983

View full text Add to dashboard Cite

show abstract

“…3, citrin, as an AGC, plays a role (1) in the supply of aspartate from the mitochondria to the cytosol and (2) as a member of the malate aspartate shuttle. The supply of aspartate formed in the mitochondria to the cytosol via AGCs is very important for urea synthesis from ammonia (Williamson 1976) and also from alanine, because oxaloacetate can be formed only in the mitochondria without reduced nicotinamide adenine dinucleotide (NADH) formation in the cytosol (Fig. 3A).…”

Section: Ctln2 and Niccd As A Citrin Deficiencymentioning

confidence: 99%

Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD)

2002

View full text Add to dashboard Cite

Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD) Abstract By using homozygosity mapping and positional cloning, we have shown that adult-onset type II citrullinemia (CTLN2) is caused by mutations of the SLC25A13 gene, which is localized on chromosome 7q21.3 and encodes a mitochondrial solute carrier protein named citrin. So far, we have reported nine mutations, most of which cause loss of citrin, and we have established several methods for DNA diagnosis. These methods have shown that more than 90% of the patients diagnosed as suffering from CTLN2 by enzymatic analysis carry SLC25A13 mutations in both alleles, indicating that CTLN2 is caused by citrin deficiency. Furthermore, by using the same DNA diagnosis methods, we discovered that 70 neonates or infants suffering from a particular type of neonatal hepatitis carry the same SLC25A13 mutations. Since the symptoms of the neonates are different from those of the more severe CTLN2 and usually ameliorate without special treatment, we designated the neonatal disease neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). We conclude that citrin deficiency causes NICCD in neonates and CTLN2 in adults through the additional effects of genetic or environmental modifiers. Since the function of citrin, together with that of an isoform, aralar, was found to be as a mitochondrial aspartate glutamate carrier, the various symptoms of NICCD and CTLN2 may be understood as caused by defective aspartate export from the mitochondria to the cytosol and defects in the malate aspartate shuttle. It is, however, still difficult to understand the cause of the hepatic deficiency of argininosuccinate synthetase protein in CTLN2.Received

show abstract

“…During the 1970s, the numerous studies on cellular Ca2+ fluxes were confined largely to movements across the membranes of isolated organelles, in particular those of the mitochondria and endoplasmic reticulum (e.g. Lehninger et al, 1967;Bygrave, 1978a;Williamson et al, 1981;Akerman and Nicholls, 1983). Initially, little attention was paid to the possible role of hormones in the control of these intracellular events, but towards the end of that decade a realization emerged that certain hormones and also cyclic AMP might play a role in the control of intracellular Ca2+ (Bygrave, 1978a;Rasmussen, 1981;Borle, 1981 ;Exton, 1981).…”

Section: Introductionmentioning

confidence: 99%

Calcium: its modulation in liver by cross-talk between the actions of glucagon and calcium-mobilizing agonists

Bygrave

Benedetti

1993

Biochemical Journal

View full text Add to dashboard Cite

Role of calcium in the hormonal regulation of liver metabolism

Cited by 316 publications

References 395 publications

Studies on the mechanism of inhibition of hepatic cAMP accumulation by vasopressin

Studies on the mechanism of inhibition of hepatic cAMP accumulation by vasopressin

Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD)

Calcium: its modulation in liver by cross-talk between the actions of glucagon and calcium-mobilizing agonists

Contact Info

Product

Resources

About